Efforts to prevent occupational health problems have been limited by the lack of reliable biomarkers that predict health effects from exposure to toxicants at work sites. We propose that the inheritance of certain polymorphic metabolizing genes that increase body burden of toxic chemical metabolites, predisposes workers to develop occupational health problems. A group of 250 petrochemical workers who have significant exposure to benzene and who have previously been surveyed will be studied to test our hypothesis. These workers will be classified into low, medium and high exposure groups, according to documented benzene-exposure health effects. Lymphocytes from these workers will be genotyped for inheritance of unfavorable polymorphic genes such as active metabolizer for CYP2D6, mutated overexpressed CYP2E1 and null genotypes for GSTM1 and GSTT1. We anticipate that the workers' relative risk for occupational diseases will be significantly associated with specific genotypes and exposure classification for benzene and enhanced by alcohol consumption and cigarette smoking. A subset of the genotyped workers will be studied to determine if expression of the CYP2E1 gene (as indicated by in vivo metabolism of chlorzosazone) will be significantly correlated with increased urine t,t-muconic acid concentrations and with increased chromosome aberrations (as determined by the fluorescence-in-situ- hybridization technique). The study will allow us to evaluate the applicaton of a new approach to identify hazards at work sites on individual workers, to improve the risk assessment process and to help guide decision making on prevention of occupational health problems.